The effects of silencing of PI3K p85α on 5-FU-induced colorectal cancer cells apoptosis

被引:7
作者
Sun, Yan [1 ]
Tian, Hua [2 ]
Wang, Lin [3 ]
Yang, Hui [4 ]
机构
[1] Guangzhou Med Univ, Dept Gastroenterol, Affiliated Hosp 3, Guangzhou 510150, Guangdong, Peoples R China
[2] Guangdong Med Coll, Houjie Hosp, Dept Gastroenterol, Dongguan 523900, Peoples R China
[3] Guang Zhou Red Cross Hosp, Dept Oncol, Guangzhou 510150, Guangdong, Peoples R China
[4] Guangdong 999 Brain Hosp, Dept Neurol, Guangzhou 510510, Guangdong, Peoples R China
关键词
PI3K p85 alpha; Colorectal cancer; Hoechst; 33258; staining; JC-1 mitochondrial membrane potential; FLUOROURACIL PLUS LEUCOVORIN; PHOSPHATIDYLINOSITOL 3'-KINASE; PATHWAY; INHIBITION; SUBUNIT; OVARIAN; GENE;
D O I
10.1007/s12032-013-0704-7
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Colorectal cancer is the third most common malignancy worldwide. 5-fluorouracil (5-FU) is the commonly used chemotherapeutic agent, however, more patients develop resistance. Phosphatidylinositol 3-kinases (PI3Ks) play a crucial role in a wide range of cellular processes associated with malignant behavior including cell growth, migration, and survival. In this study, we show increased expression of PI3K p85 alpha during the progression of colorectal cancer. Silencing of PI3K p85 alpha in colorectal cancer cells increased disruption of mitochondrial membrane potential and enhanced 5-FU-induced apoptosis. Furthermore, PI3K p85 alpha-depletion results in activated expression of apoptosis-associated genes Bcl-6, Bim, and Bax. Our results suggest that knockdown of PI3K p85 alpha is a potential therapeutic strategy in the treatment of colorectal cancer.
引用
收藏
页数:8
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共 21 条
[1]   A Randomized controlled trial of fluorouracil plus leucovorin, irinotecan, and oxaliplatin combinations in patients with previously untreated metastatic colorectal cancer [J].
Goldberg, RM ;
Sargent, DJ ;
Morton, RF ;
Fuchs, CS ;
Ramanathan, RK ;
Williamson, SK ;
Findlay, BP ;
Pitot, HC ;
Alberts, SR .
JOURNAL OF CLINICAL ONCOLOGY, 2004, 22 (01) :23-30
[2]   Comparison of oral capecitabine versus intravenous fluorouracil plus leucovorin as first-line treatment in 605 patients with metastatic colorectal cancer: Results of a randomized phase III study [J].
Hoff, PM ;
Ansari, R ;
Batist, G ;
Cox, J ;
Kocha, W ;
Kuperminc, M ;
Maroun, J ;
Walde, D ;
Weaver, C ;
Harrison, E ;
Burger, HU ;
Osterwalder, B ;
Wang, AO ;
Wong, R .
JOURNAL OF CLINICAL ONCOLOGY, 2001, 19 (08) :2282-2292
[3]   Cancer statistics, 2007 [J].
Jemal, Ahmedin ;
Siegel, Rebecca ;
Ward, Elizabeth ;
Murray, Taylor ;
Xu, Jiaquan ;
Thun, Michael J. .
CA-A CANCER JOURNAL FOR CLINICIANS, 2007, 57 (01) :43-66
[4]   Addition of bevacizurnab to bolus fluorouracil and leucovorin in first-line metastatic colorectal cancer: Results of a randomized phase II trial [J].
Kabbinavar, FF ;
Schulz, J ;
McCleod, M ;
Patel, T ;
Hamm, JT ;
Hecht, JR ;
Mass, R ;
Perrou, B ;
Nelson, B ;
Novotny, WF .
JOURNAL OF CLINICAL ONCOLOGY, 2005, 23 (16) :3697-3705
[5]   Mouse 3T3-L1 cells acquire resistance against oxidative stress as the adipocytes differentiate via the transcription factor FoxO [J].
Kojima, Takayuki ;
Norose, Takanari ;
Tsuchiya, Keita ;
Sakamoto, Kazuichi .
APOPTOSIS, 2010, 15 (01) :83-93
[6]   Insulin-like growth factor-1 prevents loss of electrochemical gradient in cardiac muscle mitochondria via activation of PI 3 kinase/Akt pathway [J].
Lai, HC ;
Liu, TJ ;
Ting, CT ;
Sharma, PM ;
Wang, PH .
MOLECULAR AND CELLULAR ENDOCRINOLOGY, 2003, 205 (1-2) :99-106
[7]   The effects of ginsenoside Rb1 on JNK in oxidative injury in cardiomyocytes [J].
Li, Jing ;
Shao, Zuo-Hui ;
Xie, Jing-Tian ;
Wang, Chong-Zhi ;
Ramachandran, Srinivasan ;
Yin, Jun-Jie ;
Aung, Han ;
Li, Chang-Qing ;
Qin, Gina ;
Vanden Hoek, Terry ;
Yuan, Chun-Su .
ARCHIVES OF PHARMACAL RESEARCH, 2012, 35 (07) :1259-1267
[8]   THE EVOLUTION OF COLORECTAL-CARCINOMA [J].
MORSON, BC .
CLINICAL RADIOLOGY, 1984, 35 (06) :425-431
[9]   Forkhead transcription factor FOXO subfamily is essential for reactive oxygen species-induced apoptosis [J].
Nakamura, Tomohiro ;
Sakamoto, Kazuichi .
MOLECULAR AND CELLULAR ENDOCRINOLOGY, 2008, 281 (1-2) :47-55
[10]   5-fluorouracil induces apoptosis in human colon cancer cell lines with modulation of Bcl-2 family proteins [J].
Nita, ME ;
Nagawa, H ;
Tominaga, O ;
Tsuno, N ;
Fujii, S ;
Sasaki, S ;
Fu, CG ;
Takenoue, T ;
Tsuruo, T ;
Muto, T .
BRITISH JOURNAL OF CANCER, 1998, 78 (08) :986-992